Preparation of polyene aldehydes



United States Patent f PREPARATION OF POLYENE ALDEHYDES Otto Isler, Marc Montavon, and Rudolf Riiegg, Basel,

Gabriel Saucy, Neuewelt-Munchenstein, and Paul Zeller, Neuallschwil, near Basel, Switzerland, assignors to Hoifmann-La Roche Inc., Nutley, N. J., a corporation of New Jersey No Drawing. Application July 2, 1956 Serial No. 595,135

Claims priority, application Switzerland July 6, 1955 17 Claims. (Cl. 260-488) The present invention relates to a process for the manufacture of 8-[2,6,6-trimethyl-cyclohexen-(l)-yl]- or 8- [2,6,6 trimethyl cyclohexylidenl or 8 [2,6,6 trimethyl cyclohexen (2) yliden] 2,6 dimethyl octatrien-(2,4,6)-al-(1) carrying an oxo, hydroxy or esterified hydroxy group in the 4-position of the cyclohexyl ring. This process comprises acetalising a 6-[2,6,6-trimethyl cyclohexen (1) yllor 6 [2,6,6 trimethylcyclohexylidenl or 6-[2,6,6-trimethyl-cyclohexen-(2)- yliden]-4-metl1yl-hexadien-(2,4)-al-(1) carrying an oxo, hydroxy or esterified hydroxy group in the 4-position of the cyclohexyl ring, condensing the resulting 4-substituted 6-[2,6,6-trimethyl-cyclohexen-(1)-yllor 6-[2,6,6- trimethyl-cyclohexylidenlor 6-[2,6,6-trimethyl-cyclohexen (2) yliden] 4 methylhexadien (2,4) acetal- (1)-with a propenyl ether in the presence of an acidic condensing agent, and treating the resulting 4-substituted 8 [2,6,6 trimethyl cyclohexen (1) yl] or 8- [2,6,6 trimethyl cyclohexylidenlor 8 8 [2,6,6- trimetbyl cyclohexen (2) yliden] -2,6 dimethyloctadien-(4,6)-ether-(3)-acetal-(1) with acidic agents to cause hydrolysis and splitting ofi of alcohol from the position 2,3.

The process may be illustrated by the following reaction scheme:

CH3 O-lower alkyl Ol0wer alkyl O-Iower alkyl ROH=(l3-CH=CHCHCH-CH CH CH3 O-lower alkyl The starting materials used in the present process, are 6 [2,6,6 trimethyl cyclohexyl] 4 methyl hexadien- (2,4)-als-(1) which are substituted in the 4-position of the cyclohexyl ring and which contain at least one additional double bond in the cyclohexyl ring or adjacent thereto. References hereinafter to substituents in the 4-position mean the 4-position of the cyclohexyl ring. The preferred starting compounds are those aldehydes which in 4-position of the cyclohexyl ring carry an oxo group. The same good results are obtained, however, if aldehydes carrying a free hydroxy group or 2,827,482 Patented Mar. 18, 1958 an esterified hydroxy group, e. g. an acetoxy group in that 4-position are used.

The first step of the process according to the present invention consists in acetalising the 4-substituted starting aldehydes. The acetalisation is carried out, e. g., by means of an ortho ester in the presence of an acidic condensing agent, such as boron trifluoride etherate, zinc chloride, ortho-phosphoric acid, p-toluenesulfonic acid, etc. The ortho esters of lower aliphatic acids with lower aliphatic alcohols, preferably methyl, ethyl or n-butyl ortho-formate, are particularly suitable.

In the preferred mode of operation the starting aldehyde is acetalised in the presence of alcohol, orthophosphoric acid and traces of p-toluenesulfonic acid by means of a lower alkyl ortho-formate. The resulting acetals are yellowish oils. In the U. V. spectrum in petroleum ether solution the 4-substituted 6-[2,6,6-trimethyl cyclohexyliden] 4 methyl hexadien (2,4)- al-(1)-acetals have absorption maxima at 276, 286 and 298 m whereas the 6-[2,6,6-trimethyl-cyclohexen-(2- yliden] 4 methyl hexadien (2,4) al (1) acetals carrying a hydroxy or esterified hydroxy group in the 4-position show absorption maxima at 317 and 331 me, and the 6- 2,6,6-trimethyl-4-oxo cyclohexen- (2) -ylidenl 4-methyl-hexadien-(2,4)-al-(1)acetal shows an absorption maximum at 340 ru The 4-substituted 6-[2,6,6- trimethyl cyclohexen (1) yl] 4 -methylhexadien- (2,4)-al-(1)-acetals show an absorption maximum in the ultraviolet spectrum at 237.5 III r. The acetals need not be purified, e. g. by distillation, prior to their further processing.

In the second step of the present process the acetals are condensed with a propenyl ether in the presence of an acidic condensing agent to form 4-substituted 8- [2,6,6 trimethyl cyclohexen (1) yl] or 8 [2,6,6- trimethyl cyclohexylidenlor 8 [2,6,6 trimethylcyclohexen- (2 -yliden]-2,6-dimethyl-o ctadien- 4,6) -ether- (3)-acetals-(l). Suitable condensing agents include boron trifluoride etherate, zinc chloride, titanium tetrachloride, aluminum chloride, ferric chloride, stannic chloride, etc. Advantageously the propenyl ether of the same alcohol with which the acetals have been prepared, e. g. methyl propenyl ether, ethyl propenyl ether or n-butyl propenyl ether, is used. The condensation is carried out at as low a reaction temperature as possible in order to avoid undesired side reactions, such as polymerisation and condensation of the formed products with propenyl ether. Depending on the condensing agent used and the acetal and propenyl ether selected for the condensation, the optimum reaction temperature is comprised between 0 and 50 C. In the preferred mode of operation approximately molecular amounts of the acetal and propenyl ether are allowed to react with each other at 20-40 C. in the presence of zinc chloride or boron trifluoride etherate. In this manner, substantially pure ether acetals are obtained in an almost quantitative yield. No particular purification, e. g. by distillation, is necessary prior to the further processing of the ether acetals.

The third step of the process according to the present invention consists in hydrolysing the obtained ether acetals in an acidic medium in a manner known per se. This reaction is preferably conducted in such a manner, e. g., by heating, that hydrolysis of the acetal groups and splitting off of alcohol from the position 2,3 take place simultaneously with formation of the 4-substituted 8- [2,6,6 trimethyl cyclohexen (1) yl]- or 8 [2,6,6-trimethylcyclohexylidenlor 8[2,6,tS-trimethyl-cyclohexen- (2)-ylidenl 2,6-dimethyl octatrien-(2,4,6)-al-(1). This reaction step is conveniently carried out in the presence of water-soluble, organic or inorganic acids, such as ptoluenesulfonic acid, acetic acid, propionic acid, oxalic acid, sulfuric acid, phosphoric acid etc., or water-soluble acid salts, such as zinc chloride and sodium bisulfate. It is advantageous to carry out the reaction with exclusion of oxygen and addition of an antioxidant such as hydroquinone. The reaction conditions are suitably selected in such a manner that the alcohol which forms during the reaction is continuously removed from the reaction mixture. A water-miscible solvent, such as dioxane, tetrahydrofurane, ethyleneglycol dimethyl ether etc., can be added to the reaction mixture in order to obtain a homogeneous mixture. Preferably, the ether acetals are heated to about 100 C. with acetic acid in the presence of an alkali acetate and some water. The reaction mixtures are conveniently diluted with water, and the products are isolated by extraction with ether. They can be purified by distillation or chromatography on alumina.

In order to avoid losses of substance due to polymerisation and decomposition, it is advisable to avoid temperatures exceeding 120 C. throughout the process and, in particular, to carry out the further processing of the intermediates, viz. the acetals and ether acetals, in the non-distilled state.

The aldehydes obtained by the process of the present invention possess characteristic absorption maxima in the ultraviolet spectrum. In view of the cis-transisomerism at the double bonds, there exists several stereo-isomeric forms of these aldehydes.

The 4-substituted 8-[2,6,6-trimethyl-cyclohexen-(1)- yl] or 8-[2,6,6-trimethyl-cyclohexyliden]- or 8-[2,6,6- trimethyl cyclohexen (2) yliden] 2,6 dimethyloctatrien-(2,4,6)-al-( 1) can be used as antioxidants. Besides, they are valuable intermediates for the synthesis of v oxygen-containing carotenoids, such as zeaxanthene, rho- They EXAMPLE 1 8 [2,6,6 trimethyl 4 acetoxy cyclohexyliden] 2,6- dimethyl-octatrien-(2,4,6)-al-(1 To a solution of 4.5 g. of 6-[2,6,6-trimethyl-4-acetoxycyclohexyliden]-4-methyl-hexadien-(2,4)-al-(l) in 4 ml. of ethyl ortho-formate there was added a mixture of 0.75 ml. of absolute alcohol and 0.075 ml. of ortho-phosphoric acid, and after the addition of 0.003 g. of p-toluenesulfonic acid the reaction mixture was allowed to stand at room temperature for 24 hours. Then 1 g. of pyridine was added, and the reaction mixture was poured into a mixture of 100 g. of sodium bicarbonate solution and g. of ice. The product was extracted with ether, and the ether solution was washed with water. After drying the ether solution over sodium sulfate and evaporation of the ether, the residue was freed from excess ethyl orthoformate in a high vacuum at 50 C. There were thus obtained 4.85 g. of acetal; U. V. absorption maxima at 286.5 and 297.5 m in petroleum ether solution. The acetal was dissolved, without any further purification, in 7 m1. of absolute benzene, 1 ml. of a 10% solution of zinc chloride in ethyl acetate was added to the solution, and then 1.2 g. of propenyl ethyl ether in 2 ml. of absolute benzene were added dropwise, while stirring and maintaining the temperature below C. The reaction mixture was then further stirred overnight at room temperature. The benzene was then removed at 30 C. in the vacuum of a water jet pump, and 20 ml. of glacial acetic acid, 1 ml. of water and 2 g. of sodium acetate were added to the residue. The mixture was heated at 95 C. for 3 hours in a carbon dioxide atmosphere. After cooling, the solution was poured into 200 ml. of water, and the reaction product was extracted with ether. The ether solution was washed several times with water and then with dilute sodium bicarbonate solution. Upon drying of the ether solution over sodium sulfate and evaporation of the ether, there were obtained 4.5 g. of 8-[2,6,6- trimethyl 4 acetoxy cyclohexyliden] 2,6 dimethyloctatrien-(2,4,6)-al-(1) in the form of a yellow tough resin; U. V. absorption maxima at 338, 354 and 372 m (in petroleum ether solution). This product can be purified by chromatography on alumina (according to Brockmann, activity state II).

The 6 [2,6,6 trimethyl 4 acetoxy cyclohexyliden]-4-methyl-hexadien-(2,4)-al-(l) required as a starting material in this example can for instance be obtained according to the following procedure:

138 g. of 2,6,6,-trimethyl-1-cyclohexen-4-one [which can be made, for example, from isophorone by known procedures; compare Kharasch, Journal of the American Chemical Society, 63, 2308 (1941)] in 50 ml. of glacial acetic acid was stirred for two hours at 0-10 C. with 160 ml. of peracetic acid (containing 530 mg. of peracetic acid per ml.) and the mixture was allowed to stand overnight at 20 C. Then, while adding ice, the reaction mixture was made weakly alkaline (pH about 8) by adding 30% aqueous NaOH solution, and the reaction mixture was shaken for one hour at 20 C. Then the mixture was extracted twice, each time with 800 ml. of diethyl ether, and the ether solutions were washed once with 200 ml. of saturated ammonium chloride solution. The ether solutions were combined and dried over sodium sulfate, the solvent was driven off, and the residue was distilled in high vacuum. A forerun passed over between 70 and C., and then 2,6,6-trimethyl-2-cyclohexen-1- ol-4-one was obtained as an almost colorless oil having B. P. -112 C.IO.1 mrn., n =l.501, U. V. maximum at 226 m (13 :1110 in petroleum ether solution), after standing for some time. The phenylsemicarbazone had M. P. 189-190", U. V. maxima at 240.5 mp and 285 m (E =807 and 778 in ethanol).

To 154 g. of2,6,6-trimethyl-2-cyclohexen-1-ol-4-one in 200 ml. of glacial acetic acid and 500 ml. of water was quickly added dropwise 70 g. of chromic anhydride in 200 ml. of water, while stirring and cooling, so that the temperature did not rise above 30 C. The mixture was then stirred overnight at 20 C. Then the reaction mixture was saturated with ammonium chloride and was extracted with 1000 ml. of petroleum ether (boiling range 3060 C.). The aqueous layer was again extracted in a second separatory funnel with 500 ml. of petroleum ether. The petroleum ether solutions were washed with saturated ammonium chloride solution to which a little ammonia had been added, and then with pure saturated ammonium chloride solution. The washed extracts were dried over sodium sulfate and the solvent was driven off. The product, 2,6,6-trimethyl-2-cyclohexene-1,4-dione, was distilled under a water pump vacuum; B. P. 9294 C.!1l mm., a yellow oil which solidified to crystalline form in the refrigerator, n =1,490, U. V. maximum at 238 mu (E =942 in petroleum ether). The phenylsemicarbazone had M. P. 190 C., then resolidified and melted again at 230 C., U. V. maxima at 242.5 me and 325.5 m (E =875 and 580 in ethanol).

65 g. of 2,6,6-trimethyl-2-cyclohexene-1,4-dione in 250 ml. of glacial acetic acid was slowly reacted with g. of zinc dust, while stirring, so that the temperature did not rise above 50 C. Then the reaction mixture was stirred for an additional period of one hour. The reaction mixture was filtered, diluted with 1000 ml. of water and then saturated with ammonium chloride. The mixture was extracted twice, each time with 800 ml. of petroleum ether (boiling range 3060 C.). The petroleum ether solutions were washed with 300 ml. of saturated ammonium chloride solution to which some ammonia was added, and then were washed with pure saturated ammonium chloride solution. (In case a portion of the product crystallizes from the petroleum ether solution, it is al n, the cr stalline material is dissolved in diasza rse ethyl ether, then the diethyl ether solution is washed as indicated above, dried over sodium sulfate and then combined with the petroleum ether solution.) The solvent was driven off until the product 2,6,6trimethyl-1,4-cyclohexanedione started to crystallize out; colorless needles, M. P. 63-65 C., having no absorption maximum in the ultraviolet spectrum between 220 and 280 m The phenylsemicarbazone had M. P. 2l8220 C., U. V. maximum at 250 m (E =1O30 in ethanol).

34.6 g. of 2,6,6-trimethyl-1,4-cyclohexanedione, 100 ml. of benzene, 19 g. of ethyleneglycol and 0.2 g. of p-toluenesulfonic acid were refluxed for seven hours while separating the water which was formed. Upon cooling, the reaction mixture was poured into 300 ml. of 5% sodium bicarbonate solution, and the 2,6,6-trimethyl-4-ethylenedioxy-l-cyclohexanone product was obtained by extraction with diethyl ether and distillation of the extract. The product was obtained as a colorless oil, having B. P. 70 C.[0.02 mm., n =1.469.

To a lithium amide suspension prepared by dissolving 6.7 g. of lithium in 2000 ml. of liquid ammonia was added slowly, while stirring, 52 g. of l-methoxy-Z-methyl- 3-butyl-2-ol. The mixture was stirred for one hour and then 79 g. of 2,6,6-trimethyl-4-ethylenedioxy-l-cyclohexanone was added, and the reaction mixture was stirred overnight at the boiling temperature of the ammonia. 60 g. of ammonium chloride was added and then the ammonia was driven ofi. The residue was taken up in diethyl ether, and insoluble material was filtered off; the ether solution was washed with a saturated solution of ammonium chloride, then was dried over sodium sulfate, and the ether was driven off. The residue was suspended in 450 ml. of petroleum ether and was extracted four times, each time was 300 ml. of 70% methanol. The methanol extracts were washed three times, each time with 150 ml. of petroleum ether, then were diluted with saturated ammonium chloride solution and the precipiated material was taken up in diethyl ether. The ether solution was washed with water, dried over sodium sulfate, and the ether was driven off. There was thus obtained 92 g. of 4-(2,6,6-trimethyl-4-ethylenedioxy-l-hydroxy-l-cyclohexyl)-2-methyl-1-methoxy-3-butyn-2-ol as a yellow, viscous oil.

92 g. of the latter was dissolved in 3000 ml. of dry diethyl ether, was mixed while stirring at 0-5 C. with a solution of 22.5 g. of lithium aluminum hydride in 300 ml. of dry diethyl ether, and the reaction mixture was refluxed for four hours. Then the reaction mixture was cooled with ice, 250 ml. of methanol was added slowly while stirring at 0-5 C., and the clear solution was poured into a mixture of 100 g. of ice and 600 ml. of saturated ammonium chloride solution. The precipitated aluminum hydroxide was filtered off and the precipitate was washed with diethyl ether and added to the filtrate. The combined liquors were washed with water, dried over sodium sulfate and the solvents were driven off. The residue was partitioned between petroleum ether and 70% methanol, in the manner indicated above, and from the methanol extracts there was obtained 70 g. of 4-(2,6,6- trimethyl 4 ethylene dioxy 1 hydroxy 1 cyclohexyl) 2 methyl 1 methoxy 3 buten 2 01 as a light yellow, viscous oil.

70 g. of the latter was mixed with 140 ml. of formic acid and the mixture was heated for minutes at 100 C. The reaction mixture was poured onto ice and extracted with diethyl ether, the ethereal solution was washed with water and with dilute sodium bicarbonate solution, dried over sodium sulfate, and the ether was driven off. The residue was dissolved in 200 ml. of glacial acetic acid, 26 ml. of water and 32 g. of sodium acetate were added, and the mixture was heated at 95 C. for two hours. Then it was diluted with ice water, and was extracted with diethyl ether, the ether extract was washed with water and with dilute sodium bicarbonate solution, dried over sodium sulfate and the ether was driven off. The residue 6 was distilled in vacuum, thereby yielding 4 (2,6,6 trimethyl 4 oxo 1 cyclohexylidene) 2 methyl 2- buten-l-al as a yellow oil having B. P. ca. 110 C. [0.02 mm., n =1.55 (U. V. maximum at 284 m in petroleum ether).

A solution of 31 g. of 4-(2,6,6-trimethyl-4-oxo-l-cyclohexylidene)-2-methyl-2-buten-l-al. in 34 ml. of orthoformic acid ethyl ester and 7 ml. of absolute ethanol was mixed with 0.65 ml. of orthophosphoric acid and 0.05 g. of p-toluene-sulfonic acid, and the mixture was allowed to stand for 24 hours at room temperature. 7 ml. of pyridine was added and then the mixture was poured upon ice and dilute sodium bicarbonate solution, the resulting mixture was extracted with petroleum ether, the petroleum ether extract was washed with water, dried over sodium sulfate, the solvent was driven off and the residue was dried in vacuo at C. There was thus obtained 40 g. of 4 (2,6,6 trimethyl 4 oxo 1 cyclohexylidene)- 2-methyl'1,l-diethoxy-Z-butene (U. V. maximum at 248 my in petroleum ether).

40 g. of the latter product was dissolved in 600 ml. of dry diethyl ether and was mixed :slowly, while stirring at 0-5 C., with a solution of 2.8 g. of lithium aluminum hydride in 40 ml. of diethyl ether. The reaction mixture was stirred for one hour at room temperature, then was cooled to 0-5 C.; 20 ml. of methanol was added slowly, and the reaction mixture was poured upon ice and saturated ammonium chloride solution. The precipitated aluminum hydroxide was filtered off and washed with diethyl ether, the ether was added to the filtrate, the combined liquors were dried over sodium sulfate and the solvent material was driven off. There was obtained 39.5 g. of 4 (2,6,6 trimethyl 4 hydroxy 1 cyclohexylidene)- 2-methyl-1,1-diethoxy-2-butene.

39.5 g. of the latter was acetylated by mixing it with 40 ml. of pyridine and 20 ml. of acetic anhydride and permitting the mixture to stand for 20 hours. The re action mixture was poured into ice water, extracted with petroleum ether, the organic layer was washed with cold sodium bicarbonate solution, dried over sodium sulfate and the solvent was driven off, yielding 42 g. of 4(2,6,6- trimethyl 4 acetoxy 1 cyclohexylidene) 2 methyl- 1,1-diethoxy-2-butene.

42 g. of the latter was mixed with 400 ml. of glacial acetic acid, 50 ml. of water and g. of sodium acetate and heated at C. for three hours. Then the reaction mixture was diluted with ice water and was extracted with diethyl ether. The ethereal solution was washed several times with water, dried over sodium sulfate and the ether was driven off. There was thus obtained 31 g. of 4-(2,6,6- trimethyl 4 acetoxy l cyclohexylidene) 2 methyl- 2-buten-1-al (U. V. maximum at 284 mp. in petroleum ether).

To a solution of 7.3 g. of 4-[2,6,6-trimethyl-4-acetoxycyclohexylidenl-2-methyl-buten-(2)-al-( 1) in 6.8 ml. of ethyl ortho-formate there was added a solution of 0.13 ml. of ortho-phosphoric acid in 1.3 ml. of absolute ethanol, and after the addition of 0.005 g. of p-toluenesulfonic acid the reaction mixture was allowed to stand at room temperature for 24 hours. Then 1.5 ml. of pyridine were added, and the reaction mixture was poured into a mixture of g. of 5% sodium bicarbonate solution and 20 g. of ice. The product was taken up in ether, and the ether extract was shaken with sodium bicarbonate solution and dried over sodium sulfate. After evaporation of the ether, the residue was freed from excess ethyl ortho-formate in a high vacuum at 50 C. There were thus obtained 7.9 g. of acetal (n =l.4965; U. V. absorption maximum at 246 m in petroleum ether solution) which was further processed without any purification. The acetal was dissolved in 10 ml. of petroleum ether (B. P. 3060 C.), 1.4 ml. of a 10% solution of zinc chloride in ethyl acetate were added to the solution, and then 1.9 g. of vinyl ethyl ether in 2 ml. of petroleum ether (B. P. 3060 C.) were slowly added dropwise, while stirring and maintaining the temperature below 30 C. The reaction mixture was then allowed to stand at room temperature for 20 hours. Thereupon, the petroleum ether was removed at 30 C. in the vacuum of a water jet pump, and 20 ml. of glacial acetic acid, 1 ml. of water and 2 g. of sodium acetate (cryst.) were added to the residue. The mixture was heated at 95 C. for 3 hours in a carbon dioxide atmosphere. After cooling, the solution was poured into 200 ml. of water, and the product was extracted with ether. The ether solution was washed several times with water and then with dilute sodium bicarbonate solution. Upon drying of the ether solution over sodium sulfate and evaporation of the ether, there were obtained 6.7 g. of 6- [2,6,6 trimethyl 4 acetoxy cyclohexyliden] 4 methyl-hexadien-(2,4)-al-(1) as a yellow viscous oil; U. V. absorption maxima at 319 and 330 ITl/L (in petroleum ether solution). The product can be purified by chromatographic adsorption on alumina (according to Brockmann, activity state II). The phenyl semicarbazone of the obtained aldehyde has absorption maxima in the U. V. spectrum at 237, 340 and 356 mg (in petroleum ether solution).

EXAMPLE 2 8- [2,6,6-trimethyl-4-0x0 cyclohexyliden] 2,6 dimelhylctatrien-(2,4,6) -al-(I) 11.5 g. of 6-[2,6,6-trimethyl-4-oxo-cyclohexyliden]-4- methyl-hexadien-(2,4)-al-(1) together with 7.5 g. of ethyl ortho-formate, 1.4 ml. of absolute alcohol, 0.14 ml. of orthophosphoric acid and 0.005 g. of p-toluenesulfonic acid were allowed to stand at room temperature for 24 hours. Then 1 ml. of pyridine was added to the reaction mixture, and the mixture was poured into 200 ml. of sodium bicarbonate solution. The product was ex tracted with ether and, upon washing the ether solution with water, drying over sodium sulfate, removal of the ether and evaporation of the excess ethyl ortho-formate in a high vacuum at 50 C., there were obtained 13.8 g. of acetal in the form of a yellowish oil; U. V. absorption maxima at 276, 286 and 298 mu (in petroleum ether solution).

The acetal was dissolved in ml. of benzene, and to the obtained solution 3.2 ml. of a 10% solution of zinc chloride in ethyl acetate were added. Then 3.85 g. of propenyl ether in 2 ml. of benzene were added drop- Wise, while stirring and maintaining the reaction temperature below C. The reaction mixture was allowed to stand over night at room temperature, and the benzene was then evaporated in the vacuum of a water jet pump at 30 C. Then ml. of glacial acetic acid, 2 ml. of water and 4 g. of sodium acetate were added to the residue, and the mixture was heated for 3 hours at 95 C. in a carbon dioxide atmosphere. After cooling, the reaction mixture was diluted with 200 ml. of water, and the product was separated by extraction with ether. The ether solution was washed several times with water and dilute sodium bicarbonate solution. After drying of the ether solution over sodium sulfate and evaporation of the ether, there were obtained 12.9 g. of 8-[2,6,6-trimethyl-4-oxocyclohexylidenl 2,6-dimethyl-0ctatrien-(2,4,6)-al-(1) in the form of a yellow viscous oil showing maxima in the U. V. absorption spectrum at 334, 350 and 370 Inn (in petroleum ether solution). The product can be purified by chromatography on thirty times its quantity of alumina (ac cording to Brockmann, activity state II).

The starting compound 6-[2,6,6-trimethyl-4-oxo-cyclohexyliden]-4-methyl-hexadien-(2,4)-al-(1) can be obtained for instance as follows:

11.5 g. of 4-[2,6,6-trimethyl-4-oxocyclohexyliden]-2- methyl-buten-(2)-al-(1) (the preparation of which is described in Example 1 above), together with 12.7 ml. of ethyl ortho-formate, 2.4 ml. of absolute ethanol, 0.24 ml. of orthophosphoric acid and 0.005 g. of p-toluene-sulfonic acid were allowed to stand at room temperature for 26 hours. Then 2 ml. of pyridine were added, and the mixturewas poured into 200 ml. of 5% sodium bicarbonate solution. The product was extracted with ether and, upon drying of the ether solution and evaporation of the ether and excess ethyl-orthoformate in a high vacuum at 50 C., there were obtained 14 g. of acetal in the form of a yellowish oil; n =1.510; U. V. absorption maximum at 248 m (in petroleum ether solution). The acetal was dissolved in 10 ml. of petroleum ether (B. P. 3060 C.) and to the obtained solution 2 ml. of a 10% solution of zinc chloride in ethyl acetate were added. Then 3.7 g. of vinyl ethyl ether in 3 ml. of petroleum ether (B. P. 3060 C.) were slowly added dropwise, while stirring and maintaining the temperature of the mixture below 30 C. The reaction mixture was allowed to stand overnight, and the petroleum ether was evaporated in the vacuum of a water jet pump at 30 C. 40 ml. of glacial acetic acid, 2 ml. of water and 4 g. of sodium acetate (cryst.) were added to the residue, and the mixture was stirred for 3 hours at C. in a carbon dioxide atmosphere. After cooling, the reaction mixture was diluted with 200 ml. of water, and the product was separated by extraction with ether. The ether solution was washed several times with water and dilute sodium bicarbonate solution. After drying and evaporation of the ether solution, there were obtained 11.5 g. of 6-[2,6,6-trimethyl-4-oxo-cyclohexyliden]-4- methyl-hexadien-(2,4)-al-(1) as a yellow viscous oil showing maxima in the U. V. absorption spectrum at 317.5 and 330 my. (in petroleum ether solution).

EXAMPLE 3 8-[2,6,6-trimethyl-4-0x0-cycl0hexelz- (2 -ylidelz]-2,6- dimethyl-0czatrien- (2,4,6)-al-(l) 22 g. of 6-[2,6,6-trimethyl-4-oxo-cyclohexen-(2)- yliden]-4-methyl-hexadien-(2,4)-al-( 1) were shaken for 3 days with 20 g. of ethyl ortho-formate, 0.4 g. of orthophosphoric acid, 6 ml. of absolute alcohol and 0.01 g. of p-toluenesulfonic acid. Then 5 ml. of pyridine were added to the reaction mixture, and the mixture was poured into a mixture of 300 ml. of 5% sodium bicarbonate solution and 20 g. of ice. The product was extracted by shaking the mixture with ether, and the ether solution was washed once with dilute sodium bicarbonate solution and once with water. After drying of the ether solution over sodium sulfate and evaporation of the ether, there were obtained 27.5 g. of acetal; U. V. absorption maximum at 340 m (in petroleum ether).

To 27 g. of the obtained acetal there were added 10 ml. of a 10% solution of zinc chloride in ethyl acetate and 0.01 ml. of boron trifluoride etherate, and then 8.5 g. of propenyl ethyl ether were slowly added dropwise to the mixture, while stirring and maintaining the reaction temperature below 30 C. The mixture was further stirred for 18 hours at room temperature. Then 250 ml. of glacial acetic acid, 15 ml. of water and 25 g. of sodium acetate were added, and the mixture was heated for 3 hours at 95 C. in a carbon dioxide atmosphere. After cooling, the reaction mixture was diluted with 2000 ml. of. water. the product was extracted with ether, and the ether solution was washed with water and dilute sodium bicarbonate solution, dried over sodium sulfate and concentrated. There were thus obtained 25 g. of a resinous crude product which, after chromatography on alumina (according to Brockmann, activity state II), yielded crystals of M. P. 141144 C.; U. V. absorption maxima at 336, 382 and 405 m (in petroleum ether solution).

The 6-[2,6,6-trimethyl-4-oxo-cyclohexen-(2)-yliden]- 4-methyl-hexadien-(2,4)-al-( 1) used as a starting material in this example can be prepared as follows:

34.6 g. of 2,6,6-trimethyl-2cyclohexene-1,4-dione (obtained as described in Example 1 above), ml. of henzene, 19 g. of ethylene glycol and 0.2 g. of p-toluenesulfonic acid were refluxed for seven hours while separating the water which was formed. Upon cooling, the reaction mixture was poured into 300 ml. of 5% sodium bicarbonate solution, and the 2,6,6-trimethyl-4-ethylenedioxy-2-cyclohexen-1-one product was obtained by extraction with diethyl ether and distillation of the extract. The product was obtained as a colorless oil, having B. P. 65 C. |0.03 mm., n =1.490, U. V. max. 225.5 m (E =560 in petroleum ether).

To lithium amide suspension prepared by dissolving 4.2 g. lithium in 500 ml. of liquid ammonia was added slowly while stirring 37 g. fl-chloro-vinyl-ethylether. The mixture was stirred for 5 minutes and then 42 g. of 2,6,6- trimethyl 4 ethylene dioxy cyclohexene-Z-one-l were slowly added, and the reaction mixture stirred for 48 hours at the boiling temperature of the ammonia. After the addition of 38 g. of ammonium chloride was completed, the ammonia was driven off. The residue was taken up in diethyl ether and insoluble material was filtered off. After decoloration of the ether solution with active charcoal, the solution was dried over sodium sulfate and the ether was driven off. There was obtained 2,6,6-trimethyl-1-hydroxy-1-ethoxyethinyl 4 ethylenedioxy-cyclohexene- 2) The 2,6,6,-trimethyl-l-hydroxy-l-ethoxyethinyl-4-ethylenedioxy-cyclohexene-(Z) was dissolved in 80 ml. of toluene and 150 ml. of petroleum ether (B. P. 80-1()O C.) and hydrogenated in the presence of 20 g. palladium-on -calcium-carbonate catalyst containing lead [Lindlar, Helvetica Chimica Acta, 35, 450 (1952)]. The catalyst was filtered otf. The solution was added with 350 ml. of 0.3 N hydrochloric acid and shaken for 20 hours under nitrogen atmosphere. The organic layer was then separated, washed with water, dried over sodium sulfate and the solvents were driven off. The residue was distilled in vacuo and recrystallized from a mixture of diethyl ether and petroleum ether. There was thus obtained 2,6,6 trimethyl-4-oxo-cyclohexen-(2)-yliden-acetaldehyde as colorless needles (M. P. 73-75 C.; U. V. maximum at 276 m in petroleum ether).

To 13 g. 2,6,6-trimethyl-4-oxo-cycylohexen-(2)-ylideneacetaldehyde suspended in 16 ml. of orthoformic acid ethyl ester were added 0.3 ml. of orthophosphoric acid, 0.01 g. of p-toluenesulfonic acid in 4 ml. of absolute ethanol. The mixture was stirred for 48 hours at room temperature. To the at present clear solution were added 3 ml. of pyridine. The mixture was poured upon a solution of 100 ml. ice-cooled sodium bicarbonate, extracted with petroleum ether, the petroleum ether extract was washed with water, dried over sodium sulfate, and the solvent was driven off. The 2,6,6-trimethyl-4-oxo-cyclohexen (2) ylidene-acetaldehyde-diethylacetal obtained (n =1.486; U. V. maximum at 270 m in petroleum ether) was added to a solution of 3 ml. of a 10% zinc chloride solution in ethylacetate and 4 drops of borontrifluorideetherate. While stirring, 7 g. of ethyl-propenylether were added slowly at a temperature of 30'35 C., the mixture was then allowed to stand for 18 hours at room temperature. To the mixture were added 200 ml. of glacial acetic acid, 10 ml. of water and 20 g. of sodium acetate. The mixture was heated for 5 hours at 95-100 C. while stirring in a nitrogen atmosphere. The reaction mixture was diluted with water, extracted with diethylether, the ether solution washed with dilute aqueous sodium bicarbonate solution, dried over sodium sulfate and the solvent was driven oif. The residue was recrystallized from methanol. There were obtained yellowish crystals of 4- [2,6,6-trimethyl-4'oxo-cyclohexen-(2)-yliden]-2-methyl-buten-(2)-al-(1) of M. P. 115-117 C.; U. V. maximum at 317 m in petroleum ether.

25.1 g. of 4-[2,6,6-trimethy1-4-oxo-cyclohexen-(2)-yliden]-2-methylbuten-(2)-al(1) were stirred for 24 hours at room temperature with 25 g. of ethyl ortho-formate 0.5 g. of ortho-phosphoric acid, 10 ml. of absolute alcohol and 0.01 g. of p-toluenesulr'onic acid. Then ml. of

pyridine were added and the mixture was poured into a mixture of 300' ml. of 5% sodium bicarbonate solution and 20 g. of ice. The product was extracted by shaking the mixture with petroleum ether (B. P. 30-60 C.), and the petroleum ether solution was washed once with dilute sodium bicarbonate solution and once with water. After drying of the petroleum ether solution over sodium sulfate and evaporation of the petroleum ether, there were obtained 32 g. of acetal; n ==l.536; U. V. absorption maximum at 316 m (in petroleum ether).

9 g. of vinyl ethyl ether and 9 ml. of a 10% solution of zinc chloride in ethyl acetate with 0.01 ml. of boron trifluoride etherate were added simultaneously at 32-34" C. to the obtained acetal, while stirring vigorously. The

' mixture was then allowed to stand at room temperature for 24 hours. Then, 250 ml. of glacial acetic acid, 15 ml. of water and 25 g. of sodium acetate (cryst) were added, and the mixture was heated for 5 hours at C., while being shaken intermittently. For isolating the product, the reaction mixture, after cooling, was poured into 2000 ml. of water, the mixture was extracted with petroleum ether (B. P. 30'-60 C.), and the petroleum ether solution was washed repeatedly with water, dilute sodium bicarbonate solution and water. After drying of the petroleum ether solution over sodium sulfate and evaporation of the petroleum ether, there were obtained 24 g. of 6-[2,6,6-trimethyl-4-oxo-cyclohexen-(2)-yliden]- 4-methyl-hexadien-(2,4)-al-(1) which partly crystallised; U. V. absorption maximum at 350-352 m (in petroleum other solution).

EXAMPLE 4 8- [2,6,6-trimethyl-4-acetoxy-cycl0hexen-(1 )-yl] 2,6-dimethyl-0cta'trien-(2,4,6)-al-(1 4.5 g. of 6-[2,6,6-trimethyl-4-acetoxy-cyclohexen-(l)- yl]-4-methyl-hexadien-(2,4)-al-(1) were treated in the manner described in Example 1. There were thus obtained 6.5 g. of 8-[2,6,6-t1 imethyl-4-acetoxy-cyclohexen- (1)-yl]-2,6-dimethyl-octatrien-(2,4,6)-al-(1) in the form of a yellow oil; U. V. absorption maximum at 310 me (in petroleum ether solution). The phenyl semicarbazone of the obtained aldehyde melted at 192-193 C., after recrystallisation;

Ei g' at 232 m 355, Ei'fi at 332 my: 1575 and 1%,, at 346 my: 1505 t The 6-[2,6,6-trimethyl-4-acetoxy-cyclohexen-( 1)-yl]-4- methyl-hexadien(2,4)-a1-(1) used. as a starting material in the process of this example can for instance be prepared as follows:

31 g. of 4-(2,6,6-trimethyl-4-acetoxy-1-cyclohexylidene)-2-methyl-2-buten-1-al (prepared according to Example 1 above) was dissolved in 40 ml. of toluene, mixed with 16 g. of isopropenyl acetate and 0.2 g. of p-toluenesulfonic acid and the mixture was heated at 140 C. while continuously removing the acetone which was formed. After approximately two hours, the reaction mixture was cooled down, poured into ice water and extracted with petroleum ether. The petroleum ether solution was washed with cold sodium bicarbonate solution and then with water, dried over sodium sulfate and the solvent was distilled off. There was thus obtained 34 g. of 4-(2,6,6-trimethyl-4-acetoxy-l-cyclohexen-l-yl)- 2-methyl-1-acetoxy-1,3-butadiene (U. V. maximum at 262 m in petroleum ether).

34 g. of the latter was dissolved in 750 ml. of methanol,

mixed with 75 ml. of water and 27 g. of sodium bicarbonate and the mixture was refluxed for six hours while stirring. Then the reaction mixture was diluted with ice water, extracted with diethyl ether, the ether solution was washed with water, dried over sodium sulfate and the ether was driven off. In order to insure acetylation of the nuclear hydroxy group, the residue, presumably containing at least some 4-(2,6,6-trimethyl-4-hydroxy-1- cyclohexen-1-yl)-2-methyl-2-buten1al, was mixed with 60 ml. of pyridine and 30 ml. of acetic anhydride and the mixture was allowed to stand for 20 hours at room temperature. 100 ml. of ice water was added and the mixture was then extracted with diethyl ether. The ethereal solution was washed with cold sodium bicarbonate solution and then with water, dried over sodium sulfate and the solvent was driven off. The 4-(2,6,6-trimethyl 4 acetoxy 1 cyclohexen l yl) 2 methyl- Z-buten-l-al thus obtained can be purified by chromatography and partitioning between solvents; U. V. maximum at 232 m in ethanol.

7.3 g. of 4-[2,6,6-trimethyl-4-acetoxy-cyclohexen-(1)- yl]-2-methyl-buten-(2)-al-( 1) were treated in the manner described in Example 1. There were thus obtained 6.8 g. of 6-[2,6,6-trimethyl-4-acetoxy-cyclohexen-(1)-yl]-4- methyl-hexadien-(2,4)-al-(l) in the form of a viscous,

yellowish oil; U. V. absorption maximum at 273-275 m (in petroleum ether solution). The phenyl semicarbazone of the obtained aldehyde, crystallised from ethyl acetate in almost colorless needles (M. P. 190 C.); U. V. absorption maxima at 234 and 304 m (in petroleum ether).

EXAMPLE 5 8- [2,6,6-trimelhyl-4-acet0xy-cycl0hexen-( 2 -ylidenl 2,6-dimethyl-octatrien-(2,4,6 -al-(I 4.5 g. of 6-[2,6,6-trimethyl-4-acetoxy-cyclohexen-(2)- yliden]-4-methyl-hexadien-(2,4)-al-( 1) were treated in the manner described in Example 1. There were thus obtained 5.9 g. of 8-[2,6,6-trimethyl-4-acetoxy-cyclohexen (2) yliden] 2,6 dimet-hyl octatrien (2,4,6)-

al-(l) which, after chromatographic purification on alumina (according to Brockmann, activity state II), formed a yellow resin; U. V. absorption maxima at 382 and 403 m (in petroleum ether solution).

The 6 [2,6,6 trimethyl 4 acetoxy cyclohexen- (2)-yliden]-4-methyl-hexadien-(2,4)-al-(l) used as start- A 48 hours at room temperature. To the clarified solution were added 5 ml. of pyridine and the solution was poured upon 200 ml. of ice-cooled sodium bicarbonate solution, then the solution was extracted with petroleum ether, the petroleum ether solution washed with water, dried over sodium sulfate and the solvent was driven off. The thus obtained 4 [2,6,6 trimethyl 4 oxo cyclohexen- (2) ylidene] 2 methyl 1,1 diethoxy buten (2) (11 =1.531; U. V. maximum at 316 m in petroleum ether solution) was dissolved in 250 ml. of absolute diethylether and was mixed slowly while stirring at 0-5 C. with a solution of 3.2 g. of lithium aluminum hydride in 80 ml. of absolute diethylether. The reaction mixture was stirred for one hour at room temperature and then was cooled to 05 C.; ml. of methanol was added slowly and poured upon ml. of saturated ammonium chloride solution. The precipitated aluminum hydroxide was filtered off and washed with diethyl ether, the ether was added to the filtrate, the combined liquors were washed with water, dried over sodium sulfate and the solvent material was driven off.

The thus obtained 4-[2,6,6-trimethyl-4-hydroxycyclohexen-(Z)-ylidene]-2-methyl-l,l-diethoxy-butene-(Z) was dissolved in ml. of pyridine mixed with 40 ml. of acetic acid anhydride and allowed to stand for 20 hours at room temperature. Then the solution was poured on ice-water,

extracted with petroleum ether and the petroleum ether solution was washed with ice-cooled sodium bicarbonate solution and with water, dried over sodium sulfate, the solvent was driven off and the residue was dried in vacuo. There was obtained 4-[2,6,6-trimethyl-4-acetoxy-cyclohexen-(2)-ylidenel-2-methyl-1,1-diethoxy-buten (2) (U. V. maximum at 282 m in petroleum ether).

10 g. of the latter were mixed with 30 g. of a solution obtained by mixing 2 g. of sodium acetate with one ml. of water and 200 ml. of glacial acetic acid. The mixture was heated for 2 hours to l00 C. under nitrogen atmosphere. The reaction mixture was cooled, poured in three times the volume of water, extracted with diethyl ether, the ether solution was washed with water, dried over sodium sulfate and the solvent material was driven off. There was obtained 4-[2,6,6-trimethyl-4-acetoxycyclohexen- 2 -ylidene]-2-methyl-buten- 2 -al-( 1) showing U. V. maximum at 310 m in petroleum ether. (M. P. of the phenylsemicarbazone l25l27 C.; U. V. maxima at 234 and 336 m in petroleum ether.)

28.8 g. of 4*[2,6,6-trimethyl-4-acetoxy-cyclohexen-(2)- yliden]-2-methyl-buten-(2)-al-(1) were treated as described in Example 3 for the compound 4-[2,6,6-trimethyl-4-oxocyclohexen- (2) -yliden] -2-methylbuten-( 2)-al by acetalisation, condensation with vinyl ethyl ether and splitting off of alcohol with glacial acetic acid in the presence of sodium acetate. There was thus obtained 25.3 g. of 6- [2,6 ,6-trimethyl-4-acetoxy-cyclohexen-(2) -yliden]- 4-methyl-hexadien-(2,4)-al-(l) in the form of a yellowish oil; U. V. absorption maxima at 353 and 372 mu (in petroleum ether solution).

We claim:

1. 1,1-di-lower alkoxy 6 [2,6,6-trimethyl4-R-cyclohexen-( l )-yl]-4-methylhexadiene-( 2,4), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

2. l,l-di-lower alkoxy 6 L2,6,6-trimetl1yl-4-R-cyclohexylidenl-4-methyl-hexadiene-(2,4), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

3. 1,1 di-lower alkoxy 6 [2,6,6-trimethyl-4-R-cyclohexen-(2)-yliden]-4methyl-hexadiene-(2,4), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

4. 1,1,3tri-lower alkoxy-S-[2,6,6-trimethyl-4-R-cyclohexen-(1)-yl]-2,6-dimethyl-octadiene- (4,6), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

5. 1,1,3-tri-lower alkoxy-8-[2,6,6-trirnethyl-4-R-cyclohexyliden]-2,6-dimethyl-octadiene-(4,6), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

6. 1,1 ,3-tri-lower alkoxy-8- 2,6,6-trimethyl-4-R-cyclohexen- 2) -yliden] -2,6-dimethyl-octadiene- 4,6 wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

7. 8-[2,6,6-trimethyl-4-R-cyclohexen (1) yl] 2,6-dimethyl-octatrien-(2,4,6)-al-(l), wherein R represents a member of the group consisting of hydroxy, lower alkonyloxy and oxo radicals.

8. 8-[2,6,6-trimethyl-4-R-cyclohexyliden]-2,6-dimethyloctatrien-(2,4,6)-al-(1), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

9. 8-[2,6,6 trimethyl-4-R-cyclohexen-(2)-yliden]-2,6- dimethyl-octatrien-(2,4,6)-al-(1), wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals.

10. 8-[2,6,6 trimethyl-4-acetoxy-cyclohexen-( l)-y1]-2, 6-dimethyl-octatrien-(2,4,6)-al-(1).

l1. 8-[2,6,6-trimethyl 4 acetoxy-cyclohexyliden]-2,6- dimethyl-octatrien-(2,4,6)-al-(1).

l2. 8-[2,6,6-trimethyl 4 acetoxy-cyclohexen-(Z)-yliden] -2,6-dimethyl-octatrien- 2,4,6 -al-( 1 13. 8-[2,6,6-trimethyl 4 oxo-cyclohexyliden] -2,6-dimethyl-octatrien- (2,4,6) -al-( 1) 14. 8-[2,6,6-trimethyl-4-oxo-cyclohexen-(2)-yliden]-2, 6-dimethyl-octatrien- (2,4,6) -al-( 1 15. A process for the manufacture of a member of the group consisting of 8-[2,6,6-trimethy1-4-R-cyc1ohexen- (1)-y1]'2,6-dimethyl-octatrien-(2,4,6) a1 (1), 8-[2,6,6- trirnethyl-4-R-cyclohexyliden1-2,6-dimethyl octatrien-(Z, 4,6)-al-(1) and 8-[2,6,6-trimethyl-4-R-cyclohexen-(2)- yliden]-2,6-dimethyl-octatrien-(2,4,6)-al-( 1 respectively, wherein R represents a member of the group consisting of hydroxy, lower alkanoyloxy and oxo radicals which comprises acetalising, respectively, with a lower alkyl orthoformate in the presence of an acetic condensing agent, a member of the group consisting of 6-[2,6,6-trimethtyl-4-R-cycloheXen-( 1 )-y11 -4-methyl-hexadien- 2,4) al-( 1 6- II2,6,6-trimethyl-4-R-cyclohexyliden] -4-methy1- hexadien-(2,4)-al-( 1) and 6-[2,6,6-trimethyl4-R-cyclo- References Cited in the file of this patent UNITED STATES PATENTS Inhofien et a1. Mar. 2, 1954 Isler et al Jan. 10. 1956 U, S. DEPARTMENT OF COMMERCE Patent no, 2,827,482

March 18, 1.958

Otto Isler et a1,

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the Patent should read as corrected below.

said Let oers Column 1, line 34, for "8==8=-[ read w 8-l e; in the reaction scheme, lines 41, 47, 54, and 59, extreme left==hand portion, for "R' in each occurrence, read Bl column 2, line 20, for "(2=" read ((2% column 3, line 26, for "exists" reed exist column 4, line 56, for

"1,490" read m 1,490 column 5, line 23, for butyle" reed =butyn line 34 for "was" read W with column 6, line 4, for "1.55" reed column ll, line 47, for "mixed O05 ml. read mixed with 0,5 ml, I column 12, line 60, for "'alkonyl read eljkenoyl= Signed and sealed this 20th day of May 1958.,

(SEAL) Attest:

KARL H, AXLINE Atteeting Officer ROBERT C. WATSON Commissioner of Patents U. S. DEPARTMENT OF COMMERCE PATENT OFFICE CERTIFICATE 0F CORRECTION Patent N0a 2327,4332 March l8, 1958 Ottolsler et aln It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the said Let ners Patent should read as corrected below. 7

Column 1, line 34 for "8=-8-=[ read 8 in the reaction scheme,

lines 41, 4'7, 54, and 59,-extreme left=he11d portion; for "R' in each occurrence, read R1 column 2 line 20, for "(2=" read (2% column 3, line 26, for "exists" read exist column 4, line 56, for "19490" read L490 column 5, line 23;, for "=butyl=" read =butyn= line 34, for "was" read with column 6, line 4, for "1055" read m 1555 column 11, line 4'7, for "mixed O05 mlc" read mixed with 005 mlo column 12;, line 60, for "alkonyl=" read aljaanoyl= =-=a Signed and sealed this 29th day of May 19580 (semi Atteet: KARL HO AXLINE ROBERT C. WATSON Attesting Officer Comissioncr of Patents U. 5. DEPARTMENT OF COMMERCE PATENT OFFICE CER'HFECATE 0F CGRRECTION Patent Noe 2 82'7,482 March 18, 1958 Otto-Isler et aln It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the said. Let oers Patent should read as corrected below Column 1, line 34,, for 8= 8=-[" read 84; g in time reaction scheme, lines 41 .47, 51;, and 59 extreme left==hand portion, for "3 in each occurrence read R'- column 2, line 2Q for "(2=" reed (2) column 3, line 26, for "exists" reed exist column 4 line 56, for "1 4%" read m 1 490 colwnn 5, line 23, for "=butyl=" reed ==but line 34, for "was" read with column 6, line 4 for "1055" read as 1555 column 11 line 4'7 for "mixed 005 11:14," read mixed With C 05 mlu g column l2; line 60, for "elkonyl read elkanoyl= ===D Signed and sealed this 20th day of May 19580 Attest:

Kiel in t ROBERT c. WATSON Attcsting Officerf Ccmissioner of Patents 

1. 1,1-DI-LOWER ALKOXY-6-(2,6,6-TRIMETHYL-4-R-CYCLOHEXEN-(1)-YL)-4-METHYL-HEXADIENE-(2,4), WHEREIN R REPRESENTS A MEMBER OF THE GROUP CONSISTING OF HYDROXY, LOWER ALKANOYLOXY AND OXO RADICALS.
 15. A PROCESS FOR THE MANUFACTURE OF A MEMBER OF THE GROUP CONSISTING OF 8-(2,6,6-TRIMETHYL-4-R-CYCLOHEXEN(1)-YL) 2,6-DIMETHYL-OCTATRIEN-(2,4,6)-AL-(1), 8-(2,6,6TRIMETHYL-4-R-CYCLOHEXYLIDEN)-2,6-DIMETHYL - OCTATRIEN-(2, 4,6)-AL-(1) AND 8-(2,6,6-TRIMETHYL-4-R-CYCLOHEXEN-(2)YLIDEN)-2,6-DIMETHYL-OCTATRIEN-(2,4,6) -AL-(1), RESPECTIVELY, WHEREIN R REPRESENTS A MEMBER OF THE GROUP CONSISTING OF HYDROXY, LOWER ALKANOYLOXY AND OXO RADICALS WHICH COMPRISES ACETALISING, RESPECTIVELY, WITH A LOWER ALKYL ORTHOFORMATE IN THE PRESENCE OF AN ACETIC CONDENSING AGENT, A MEMBER OF THE GROUP CONSISTING OF 6-(2,6,6-TRIMETHYL-4-R-CYCLOHEXEN-(1)-YL)-4-METHYL-HEXADIEN-(2,4)AL-(1), 6-(2,6,6-TRIMETHYL-4-R-CYCLOHEXYLIDEN)-METHYLHEXADIEN-(2,4)-AL-(1) AND 6-(2,6,6-TRIMETHYL-4-R-CYCLOHEXEN-(2)-YLIDEN)-4-METHYL-HEXADIEN-(2,4)-AL -(1), WHEREIN R HAS THE SAME SIGNIFICANCE SET FORTH ABOVE, CONDENSING THE RESULTING ACETAL AT 0 TO 50*C. WITH A PROPENYL LOWER ALKYL ETHER IN THE PRESENCE OF AN ACIDIC CONDENSING AGENT AND TREATING THE ETHER-ACETAL THUS OBTAINED WITH AN ACIDIC AGENT TO HYDROLYZE AND SPLIT OFF ALCOHOL FROM THE 2,3-POSITION. 